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Core F: Biomarker

核心 F：生物标志物

基本信息

批准号：
10164700
负责人：
Celeste Marie Karch
金额：
$ 26.41万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-05-15 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10164700
关键词：
3-Dimensional Affect Age Alzheimer&apos s Disease Alzheimer&apos s disease model Alzheimer&apos s disease related dementia Alzheimer&apos s disease risk Alzheimer’s disease biomarker Apolipoprotein E Architecture Area Astrocytes Biological Assay Biological Markers Biological Models Biological Process Biopsy Brain Budgets C9ORF72 Cell Line Cells Charge Clinical Cognition Collaborations Collection Communities Database Management Systems Dermal Disease European Family Family history of Fibroblasts Frontotemporal Lobar Degenerations Future Gene Expression Genetic Genomics Goals Grant Human Human Genome Idiopathic Parkinson Disease Image Individual Induced pluripotent stem cell derived neurons Inherited Laboratories Late Onset Alzheimer Disease Link Liquid substance Magnetic Resonance Imaging Medical Genetics Microglia Molecular Molecular Analysis Mutation Neurodegenerative Disorders Neurons Oligodendroglia Organoids Parkinson Disease Participant Pathogenesis Pathologic Pathology Phase Population Positron-Emission Tomography Process Program Research Project Grants Research Research Personnel Resources Sampling Services Skin Somatic Cell TREM2 gene Variant Work age related autosomal dominant Alzheimer&apos s disease biobank brain tissue cell type cohort data management data sharing disorder risk drug discovery ethnic diversity genetic architecture genome editing human stem cells induced pluripotent stem cell neuropathology novel novel marker presenilin-1 presenilin-2 protein aggregation rare variant risk variant specific biomarkers statistics stem cell model stem cells tool transcriptome

项目摘要

Core F: Biomarker Project Summary Neurodegenerative diseases result from multifactorial processes that cause pleiotropic changes in the molecular networks that link a host of biological processes, leading to protein aggregation in the brain, and ultimately to the relentless decline in cognition that characterizes most age-related dementing illnesses. Neurodegenerative diseases, such as Alzheimer disease (AD), idiopathic Parkinson's disease (PD), and frontotemporal lobar degeneration (FTLD) occur by mechanisms in which common or rare variants associated with disease risk are directly inherited or arise sporadically. Human somatic and stem cell models have emerged as a powerful system for modeling the complexities of pathological gene expression, particularly in the early phase of disease, in the context of a non-neoplastic human genome. Further, human stem cells can be differentiated into individual cell types affected in disease, such as neurons, astrocytes, microglia, and oligodendrocytes, as well as 3D “mini-brain” organoids. To this end, we have established a biorepository of stem cell models of AD and related dementias. The collection includes more than 200 human fibroblasts from the Knight ADRC and the Dominantly Inherited Alzheimer Network (DIAN) and induced pluripotent stem cell (iPSC) lines from more than 30 individuals carrying mutations in APP, PSEN1, PSEN2, GRN, MAPT, and risk variants in MAPT, APOE, TREM2, RAB10 and PLD3. Our long-term goal is to develop a set of tools and biomarkers for AD and related dementias. To do this, we will continue to build a biorepository of human somatic and stem cell models. These cells will facilitate the study of basic disease mechanisms, allow for discovery of novel biomarkers, and facilitate drug discovery platforms. We will focus on cell collection that builds on three major areas of strength in the Knight ADRC: (1) contributions of diverse ethnic backgrounds to molecular and cellular biomarkers of AD; (2) genetic and molecular modifiers of age at onset in large families with a dense family history of late onset AD; and (3) comparison of the molecular and cellular biomarkers that are common and unique between autososomal dominant AD and sporadic, late onset AD. Finally, we will make available the human somatic and stem cell lines to the broader research community to revolutionize our understanding of AD and related dementias.

核心F：生物标志物项目总结